Allergic airway inflammation affects almost 300 million people worldwide, with up to 11% of the population of the United States alone, and its rate continues to increase in urbanized countries. Due to the lack of knowledge of the molecular and cellular basis of allergic airway inflammation, there is no cure for this disease, making it one of the most expensive diseases for healthcare systems in developed countries. This makes our work highly significant. Allergic asthma is characterized by an elevated production of inflammatory cytokines such as IL-4 (produced by Th2 cells) and IL-17 (by Th17 cells), which are subjected to counter regulation by Foxp3+ T regulatory (Treg) cells and Foxp3- IL-10+ type 1 regulatory T (Tr1) cells. Being able to manipulate the development of pathogenic and regulatory T cells is a potentially promising immunotherapeutic strategy for controlling and suppressing such lung inflammation. We have found that activation of the amino acid sensor kinase GCN2 significantly enhances the development of Tr1 cells. By contrast, it has been reported that activation of the GCN2 pathway suppresses Th17 differentiation in certain autoimmune diseases, but has minimal effects on Th2 and Treg cell development, although the mechanism remains unclear. Based on these results, we hypothesize that the GCN2 pathway counter regulates the development of Tr1 and Th17 cells during allergic airway inflammation. We propose experiments in two specific aims that will determine the role of GCN2 in the development of Tr1 and Th17 cells in mice and human, and mechanism(s) through which it does so. This work is extremely innovative as we utilize novel transgenic mice, well-established approaches and a pharmaceutically validated compound, and have exciting preliminary data that will be expanded to provide information on a signaling pathway that could be used to manipulate the development of Tr1 and Th17 cells during lung inflammation as well as other inflammatory conditions.